title: Neuromodulatory propensity of Bacopa monniera against scopolamine-induced cytotoxicity in PC12 cells via down-regulation of AChE and up-regulation of BDNF and muscarnic-1 receptor expression.
abstract: Scopolamine is a competitive antagonist of muscarinic acetylcholine receptors, and thus classified as an anti-muscarinic and anti-cholinergic drug. PC12 cell lines possess muscarinic receptors and mimic the neuronal cells. These cells were treated with different concentrations of scopolamine for 24 h and were protected from the cellular damage by pretreatment with Bacopa monniera extract (BME). In current study, we have explored the molecular mechanism of neuromodulatory and antioxidant propensity of (BME) to attenuate scopolamine-induced cytotoxicity using PC12 cells. Our results elucidate that pretreatment of PC12 cells with BME ameliorates the mitochondrial and plasma membrane damage induced by 3 μg/ml scopolamine to 54.83 and 30.30 % as evidenced by MTT and lactate dehydrogenase assays respectively. BME (100 μg/ml) ameliorated scopolamine effect by down-regulating acetylcholine esterase and up-regulating brain-derived neurotropic factor and muscarinic muscarinic-1 receptor expression. BME pretreated cells also showed significant protection against scopolamine-induced toxicity by restoring the levels of antioxidant enzymes and lipid peroxidation. This result indicates that the scopolamine-induced cytotoxicity and neuromodulatory changes were restored with the pretreatment of BME.
authors.affiliation: Biochemistry and Nanosciences Discipline, Defence Food Research Laboratory, Siddarthanagar, Mysore, 570011, India.
authors.forename: M D
authors.initials: MD
authors.lastname: Pandareesh
authors.forename: T
authors.initials: T
authors.lastname: Anand
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D034681:Bacopa / Q000737:chemistry*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000235:genetics* / Q000378:metabolism; D012601:Scopolamine / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D010936:Plant Extracts; D011976:Receptors, Muscarinic; D012601:Scopolamine; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D000110:Acetylcholinesterase; D005978:Glutathione